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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 253 records · Page 14Linked to original sources
PubMed1999

New drugs for BNCT: an experimental approach.

New kinds of boron-containing drugs were developed and tested in several murine tumor models. The boron-containing ether lipid B-Et-11-OMe was injected in mammary carcinoma (AT17) and osteosarcoma (OTS-64) bearing mice. Furthermore boron-substituted ferrocenium derivatives were tested. Two were excessively toxic; the third could be investigated. Boron accumulation and time-dependent biodistribution were determined using alpha-particle sensitive films and inductively coupled plasma-atomic emission pectrometry (ICP-AES) and -mass spectrometry (ICP-MS) of tumors, organs and tissues. Additionally, a new method of boron detection by NMR is in preparation.

Animals↗
PubMed1999

[Reoperations for persistent or recurrent hyperparathyroidism].

Reoperations for persistent or recurrent primary or secondary hyperparathyroidism are demanding tasks mainly when localization of parathyroid tumor(s) was not successful. These procedures may harbor a risk for the patients and therefore need an expert surgeon who is familiar with even the most difficult situation. Important steps before surgery are confirmation of the diagnosis of persistent or recurrent disease and localization of the source of hormone access. Reoperations should be exclusively performed in centers where expert surgeons, radiologists, endocrinologists and nephrologists are available, as well as special technical equipment.

Adenoma↗
PubMed1999

[Neurinoma of the major petrosus nerve].

Facial nerve schwannomas are rare benign tumors, when occurring, they are located most frequently in the distal fallopian canal and present as extracranial masses. The predominant symptom is a progressive facial nerve paralysis. We report a 20-year-old woman with an intracranial schwannoma originating from the greater superficial petrosal nerve that had wide extension into the pterygopalatine fossa. The motor facial nerve including the geniculate ganglion was not affected. The patient presented with vertigo, progressive hearing loss and mild facial nerve synkinesis but without a lacrimation deficit. The tumor was detected by computed tomography and magnetic resonance imaging. The schwannoma was completely removed using an intracranial, extradural middle fossa approach during which complete preservation of the motor facial nerve was possible. To our knowledge this is the first reported case of an isolated schwannoma of the greater superficial petrosal nerve without involvement of the motor facial nerve.

Adult↗
PubMed1999

[Sjögren syndrome and bilateral MALT lymphoma of the parotid gland].

Sjögren's syndrome is an important autoimmune disease in the head and neck. Patients have an increased arrival risk of up to 6% per year for developing B-cell lymphomas, including mucosa-associated lymphoid tissue (MALT) lymphomas. The following case report shows this relation and the difficulty of differentiating clinically recurrent swelling of the parotid gland in Sjögren's syndrome from malignant lymphoma. A 64-year-old woman had a 2-year history of indolent, recurrent swelling of both parotid glands. Blood examination showed elevated ESR and a hypergammaglobulinemia. Immunosuppressive therapy produced no improvement. Two years after the diagnosis of Sjögren's syndrome, swelling of the left parotid gland persisted. Superficial parotidectomy of the left side was performed and histopathological examination revealed a MALT-related lymphoma. Subsequent parotidectomy of the right side also showed infiltration of the gland by a MALT lymphoma. Postoperative radiation therapy was given. During the follow-up period no recurrence or systemic disease was detected. Patients with Sjögren's syndrome should be examined regularly by the otolaryngologist. If a lymphoma cannot be ruled out, open biopsy must be considered for histological diagnosis. Prognostic factors for developing a lymphoma are possibly a high ESR and hypergammaglobulinemia. Further prognostic factors have to be evaluated.

Blood Sedimentation↗
PubMed1999

[Subtotal spinal cord dissection from a stab injury].

We report a stab-injury of the back with consecutive dissection of a thoracic vertebral arch and subtotal dissection of the spinal cord. The clinical findings and out-come of the patient--representing an incomplete Brown-Sequardsyndrome--are described. The diagnostic and therapeutic management of such rare entities is discussed.

Adult↗
PubMed1999

[Genetics of schizophrenic disorders. New concepts and findings].

Schizophrenia is a genetic complex disease as it does not follow monogenic transmission while non-familial environmental factors have a strong additional impact. A heterogeneous, continuous phenotype is transmitted in families which can now be more precisely characterized. Genes coding for proteins with presumed pathophysiological relevance are apparently not playing a major causal role. However, in the last three years several (currently seven) candidate regions have been identified in a replicable manner by linkage studies. These regions are likely to host susceptibility genes for schizophrenia, but none of them has been identified up to now. Given these findings, polygenic transmission has now become very likely. The candidate regions are currently being narrowed down by various promising techniques.

Biomarkers↗
PubMed1999

On identification of Na(+) channel gating schemes using moving-average filtered hidden Markov models.

Transitions between distinct kinetic states of an ion channel are described by a Markov process. Hidden Markov models (HMM) have been successfully applied in the analysis of single ion channel recordings with a small signal-to-noise ratio. However, we have recently shown that the anti-aliasing low-pass filter misleads parameter estimation. Here, we show for the case of a Na(+) channel recording that the standard HMM do neither allow parameter estimation nor a correct identification of the gating scheme. In particular, the number of closed and open states is determined incorrectly, whereas a modified HMM considering the anti-aliasing filter (moving-average filtered HMM) is able to reproduce the characteristic properties of the time series and to perform gating scheme identification.

Cell Line↗
PubMed1999

NF-kappaB/Rel activation in cerulein pancreatitis.

BACKGROUND & AIMS: Recent evidence suggests that a number of rapid signaling cascades are initiated during secretagogue-induced pancreatitis. However, little is known about the nuclear events. The aim of this study was to explore activation of the transcription factor NF-kappaB/Rel after supramaximal stimulation with the cholecystokinin analogue cerulein in the pancreas. METHODS & RESULTS: Nuclear appearance of NF-kappaB/Rel-binding activity was detectable 15 minutes after cerulein injection. The DNA-binding activity consisted of NF-kappaB1 p50, NF-kappaB2 p52, and RelA p65 as judged by supershift assays and Western blot analysis. The onset and termination of NF-kappaB/Rel activation correlated with the degradation and reappearance of IkappaBalpha. Cerulein in supramaximal but not in physiological doses activated NF-kappaB/Rel in vitro. After blocking of NF-kappaB/Rel activation with pyrrolidine dithiocarbamate, the degree of morphological alterations was more pronounced than in controls, serum amylase and lactate dehydrogenase levels were significantly increased, and messenger RNA levels of pancreatitis-associated protein were more strongly induced, reflecting a more severe degree of pancreatitis. Similar results were obtained when N-acetyl-L-cysteine was used as an inhibitor of NF-kappaB activation. CONCLUSIONS: These data show that NF-kappaB/Rel is rapidly activated during cerulein pancreatitis. This activation may induce a self-defending genetic program before the onset of cellular injury, which might prevent higher degrees of damage of pancreatic acinar cells after secretagogue hyperstimulation.

Acetylcysteine↗
PubMed1999

Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits.

Apoptotic macrophages are regularly found in atherosclerotic plaques indicating programmed cell death as one of their regulatory controls. The objective of this study was to characterize in more detail apoptotic macrophages in atherosclerotic lesions of humans and heritable hyperlipidemic (HHL) rabbits. Macrophages were immunohistochemically analyzed using antibodies directed against alphaMbeta2-integrins (CD11b/CD18), CD44, major histocompatibility complex (MHC) class I and II, inducible nitric oxide synthase (iNOS), manganese superoxide dismutase (MnSOD), tumor necrosis factor alpha (TNFalpha), p53, c-jun/AP-1 and rabbit macrophages (RAM-11) and the TUNEL (TdT-mediated dUTP nick end labeling) technique. Colocalization studies of human atherosclerotic carotid and aortic tissue showed apoptotic plaque macrophages also being MnSOD-, alphaMbeta2-integrin-, CD44-, MHC class I- and II-, iNOS-, TNFalpha- and p53-immunoreactive. Similar results occurred in atherosclerotic aortas of HHL rabbits. Computer-assisted morphometric analyses revealed a positive correlation of the area density of MnSOD-immunoreactive macrophages with those of alphaMbeta2-integrin- and CD44-immunoreactive ones, but not with those of MHC class I- and II- as well as of RAM-11-immunoreactive macrophages. We conclude that apoptotic macrophages located in atherosclerotic vessel wall are activated, antigen-presenting, integrin-expressing and oxidatively stressed cells. Since all these processes have been demonstrated to cause apoptosis of macrophages in vitro, we propose their potency accelerates the susceptibility of the macrophages to programmed cell death in atherosclerotic lesions.

Animals↗
PubMed1999

The domain-specific probe EUB338 is insufficient for the detection of all Bacteria: development and evaluation of a more comprehensive probe set.

In situ hybridization with rRNA-targeted oligonucleotide probes has become a widely applied tool for direct analysis of microbial population structures of complex natural and engineered systems. In such studies probe EUB338 (AMANN et al., 1990) is routinely used to quantify members of the domain Bacteria with a sufficiently high cellular ribosome content. Recent reevaluations of probe EUB338 coverage based on all publicly available 16S rRNA sequences, however, indicated that important bacterial phyla, most notably the Planctomycetales and Verrucomicrobia, are missed by this probe. We therefore designed and evaluated two supplementary versions (EUB338-II and EUB338-III) of probe EUB338 for in situ detection of most of those phyla not detected with probe EUB338. In situ dissociation curves with target and non-target organisms were recorded under increasing stringency to optimize hybridization conditions. For that purpose a digital image software routine was developed. In situ hybridization of a complex biofilm community with the three EUB338 probes demonstrated the presence of significant numbers of probe EUB338-II and EUB338-III target organisms. The application of EUB338, EUB338-II and EUB338-III should allow a more accurate quantification of members of the domain Bacteria in future molecular ecological studies.

Bacteria↗
PubMed1999

N30 and the effect of explorative finger movements: a model of the contribution of the motor cortex to early somatosensory potentials.

OBJECTIVES: The source of the N30 potential in the median nerve somatosensory evoked potentials (SEP) has been previously attributed to a pre-central origin (motor cortex or the supplementary motor area, SMA) or a post-central located generator (somatosensory cortex). This attribution was made from results of lesion studies, the behavior of the potential under pathological conditions, and dipole source localization within spherical volume conductor models. METHODS: The present study applied dipole source localization and current density reconstruction within individual realistically shaped head models to median nerve SEPs obtained during explorative finger movements. RESULTS: The SEPs associated with movement of the stimulated hand showed a minor reduction of the N20 amplitude and a markedly reduced amplitude for the frontal N30 and parietal P27, exhibiting a residual frontal negativity around 25 ms. The brain-stem P14 remained unchanged. Mapping of the different SEPs (movement of the non-stimulated hand minus movement of the stimulated hand) showed a bipolar field pattern with a maximum around 30 ms post-stimulus. In eight out of ten normal subjects, both the N30 and the gN30 (subtraction data) sources resided within the pre-central gyrus, more medially than the post-centrally located N20. Two subjects, in contrast, showed rather post-centrally localized sources in this time range. A model of the cortical SEP sources is introduced, explaining the data with respect to previously described findings of dipole localization, and from lesion studies and the alterations seen in motor diseases. CONCLUSIONS: The results provide evidence for a pre-central N30 generator, predominantly tangentially oriented, located within the motor cortex, while no sources were detected elsewhere. It is suggested that the mechanisms underlying the 'gating' effect during explorative finger movements in the 30 ms time range predominantly arise in the motor cortex.

Adult↗
PubMed1999

Turban tumour with involvement of the parotid gland.

Familial autosomal dominant cylindromatosis (FADC, turban tumour syndrome, Brooke-Spiegler-syndrome and many more, MacKusick catalogue numbers 123850, 313100) is a rare hereditary disease usually presenting in the second or third decade. With female preponderance dermal cylindromas predominantly arise in hairy areas of the body with approximately 90 per cent on the head and neck. Transformation to malignancy seems to be scarce. Although cylindromas of the skin resemble basal cell adenomas of the salivary gland, there is usually no salivary gland involvement. On the other hand, patients with basal cell adenomas of a salivary gland usually do not show dermal lesions. We report one of the rare cases of FADC combined with multiple basal cell adenomas of the parotid glands and present a review of the literature.

Adenoma↗
PubMed1999

A pharmacokinetic/pharmacodynamic approach to predict the cumulative cortisol suppression of inhaled corticosteroids.

The suppression of endogenous cortisol release is one of the major systemic side effects of inhaled corticosteroids in the treatment of asthma. The circadian rhythm of the endogenous cortisol release and the resulting plasma concentrations as well as the release suppression during corticosteroid therapy could previously be described with an integrated PK/PD model. Based on this model, a PK/PD approach was developed to quantify and predict the cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. The presented method was applied to predict CCS after single doses and during short-term multiple dosing of the inhaled corticosteroids flunisolide (FLU), fluticasone propionate (FP), and triamcinolone acetonide (TCA), and after oral methylprednisolone as systemic reference therapy. Drug-specific PK and PD parameters were obtained from previous single-dose studies and extrapolated to the multiple-dose situation. For single dosing, a similar CCS within the range of 16-21% was predicted for FP 250 micrograms, FLU 500 micrograms, and TCA 1000 micrograms. For multiple dosing, a respective CCS of 28-33% was calculated for FLU 500 micrograms bid, FP 250 micrograms, bid, and TCA 1000 micrograms bid. Higher cortisol suppression compared to these single and multiple dosing regimens of the inhaled corticosteroids was predicted after oral doses of only 1 mg and 2 mg methylprednisolone, respectively. The predictive power of the approach was evaluated by comparing the PK/PD-based simulations with data reported previously in clinical studies. The predicted CCS values were in good correlation with the clinically observed results. Hence, the presented PK/PD approach allows valid predictions of CCS for single and short-term multiple dosing of inhaled corticosteroids and facilitates comparisons between different dosing regimens and steroids.

Administration, Inhalation↗
PubMed1999

Investigation of female survival benefit in metastatic melanoma.

Epidemiological studies show female survival benefit in advanced metastatic melanoma. In investigating a possible mechanism for this female survival benefit, we have previously reported that the female steroid 17beta-oestradiol significantly reduces invasion of a human melanoma cell line (A375-SM cells) and ocular melanoma cells through fibronectin. Neither cell type was found to possess oestrogen receptor-alpha. The aim of the current study was to obtain further information on the extent to which progression of cutaneous melanoma might be sex steroid sensitive by (a) examining the relationship between circulating sex steroids, sex hormone binding globulin and disease progression; (b) examining the relationship between sex steroid structure and the ability of steroids to reduce invasion of a melanoma cell line in vitro; and (c) examining the effects of sex steroids on proliferation of these cells in vitro. We report a significant reduction in circulating oestrone with disease progression in male but not female patients. Examining steroids for their ability to inhibit invasion of A375-SM cells through fibronectin in vitro, oestrogenic compounds (17beta-oestradiol and oestrone) were found to inhibit invasion; in this respect, oestrone was approximately 50 times more potent than 17beta-oestradiol; steroids lacking the benzene ring structure did not inhibit invasion, indeed dehydroepiandrosterone (DHEA) which acts as a precursor to androgenic steroids significantly enhanced invasion. Proliferation of A375-SM cells was unaffected by 17beta-oestradiol, oestrone or dihydrotestosterone when cells were cultured on plastic; in contrast, all three steroids induced modest proliferation of cells when grown on fibronectin with dihydrotestosterone the most mitogenic of the three steroids. These data are consistent with sex steroids playing a role in melanoma progression.

Adolescent↗
PubMed1999

Substrate-specific selenoprotein B of glycine reductase from Eubacterium acidaminophilum. Biochemical and molecular analysis.

The substrate-specific selenoprotein B of glycine reductase (PBglycine) from Eubacterium acidaminophilum was purified and characterized. The enzyme consisted of three different subunits with molecular masses of about 22 (alpha), 25 (beta) and 47 kDa (gamma), probably in an alpha 2 beta 2 gamma 2 composition. PBglycine purified from cells grown in the presence of [75Se]selenite was labeled in the 47-kDa subunit. The 22-kDa and 47-kDa subunits both reacted with fluorescein thiosemicarbazide, indicating the presence of a carbonyl compound. This carbonyl residue prevented N-terminal sequencing of the 22-kDa (alpha) subunit, but it could be removed for Edman degradation by incubation with o-phenylenediamine. A DNA fragment was isolated and sequenced which encoded beta and alpha subunits of PBglycine (grdE), followed by a gene encoding selenoprotein A (grdA2) and the gamma subunit of PBglycine (grdB2). The cloned DNA fragment represented a second GrdB-encoding gene slightly different from a previously identified partial grdBl-containing fragment. Both grdB genes contained an in-frame UGA codon which confirmed the observed selenium content of the 47-kDa (gamma) subunit. Peptide sequence analyses suggest that grdE encodes a proprotein which is cleaved into the previously sequenced N-terminal 25-kDa (beta) subunit and a 22-kDa (alpha) subunit of PBglycine. Cleavage most probably occurred at an -Asn-Cys- site concomitantly with the generation of the blocking carbonyl moiety from cysteine at the alpha subunit.

Amino Acid Oxidoreductases↗
PubMed1999

Accidental cell death and generation of reactive oxygen intermediates in human lymphocytes induced by thionins from Viscum album L.

The cytotoxic mechanisms of thionins from Viscum album L., the viscotoxins, were investigated in human granulocytes and lymphocytes. The time course of viscotoxin effects indicate accidental cell death, i.e. membrane permeabilization, degradation of cytoplasm and chromatin, swelling of mitochondria with loss of their cristae, and generation of reactive oxygen intermediates within 1-2 h, followed by secondary apoptosis-associated events. The viscotoxin homologue purothionin from whole-wheat flour and viscotoxin B, however, did not induce cell death in cultured lymphocytes. Cytotoxicity of cationic and amphipathic viscotoxin was prevented only by cleavage of its disulphide bridges.

Apoptosis↗